{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:41:07Z","timestamp":1792708867849,"version":"4.5.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Evidence of the diverse genetic architecture of dilated cardiomyopathy (DCM) continues to emerge and requires reassessment of the clinical relevance of implicated disease genes. Building on the 2019-2020 Clinical Genome Resource evaluation, the DCM gene curation expert panel reconvened in 2024-2025 to conduct a reassessment of genes in DCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>The Clinical Genome Resource semiquantitative clinical validity classification framework was applied with specifications to DCM to classify genes into categories on the basis of strength of published evidence for a DCM phenotype. Previously curated genes were reassessed, and newly reported gene\u2013disease\u2013mode of inheritance (MOI) relationships, termed \u201ccurations,\u201d were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Sixty-eight genes were evaluated, inclusive of 72 unique gene-disease-MOI relationships across 51 previously evaluated and 17 newly assessed genes. Thirty-five curations were classified as high evidence (16 Definitive, 10 Strong, 9 Moderate), increasing by 16 from the prior assessment. Nine newly assessed genes were classified as high evidence:\n                      <jats:italic toggle=\"yes\">BAG5<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">FLII<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">LMOD2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">MYLK3<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">MYZAP<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">NRAP<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">PPA2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">PPP1R13L<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">RPL3L<\/jats:italic>\n                      . Twelve genes (11 newly appraised) were rated as high evidence with an autosomal recessive (AR) MOI. Five reevaluated genes from 2019-2020 had clinically significant changes in classification. Except for\n                      <jats:italic toggle=\"yes\">JPH2<\/jats:italic>\n                      , for which curation was modified to separate autosomal dominant and AR MOI curations, clinically significant changes involved upgrades from low- to high-evidence categories (\n                      <jats:italic toggle=\"yes\">PLEKHM2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">PRDM16<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">TBX20<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">TNNI3K<\/jats:italic>\n                      ), demonstrating the robustness of the Clinical Genome Resource gene curation process over time. An additional 29 gene-disease-MOI curations were classified as Limited, including 6 newly evaluated genes and 1 new MOI for a previously evaluated gene,\n                      <jats:italic toggle=\"yes\">MYBPC3<\/jats:italic>\n                      -AR; 4 were classified as No Known Disease Relationship, and remained Disputed. Four previously evaluated genes were curated for both AD and AR MOIs:\n                      <jats:italic toggle=\"yes\">JPH2<\/jats:italic>\n                      (AD-Strong, AR-Limited),\n                      <jats:italic toggle=\"yes\">LDB3<\/jats:italic>\n                      (AD-Limited, AR-Strong),\n                      <jats:italic toggle=\"yes\">MYBPC3<\/jats:italic>\n                      (AD-Limited, AR-Limited), and\n                      <jats:italic toggle=\"yes\">TNNI3<\/jats:italic>\n                      (AD- and AR- Strong).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>With substantial new evidence, the genetic architecture of DCM has rapidly expanded. This updated assessment of genes reported in DCM yielded 35 high-evidence curations, an increase from 19 only 5 years ago. The results of this evidence-based evaluation process inform clinical interpretation of genetic information in the care of DCM patients and families.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.126.080302","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:01:55Z","timestamp":1788858115000},"page":"1592-1603","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["An Updated Evidence Assessment of the Genetic Causes of Dilated Cardiomyopathy"],"prefix":"10.1161","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2073-3258","authenticated-orcid":true,"given":"Elizabeth","family":"Jordan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phoenix","family":"Grover","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Hospital, Durham, NC 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